Capecitabine ON Temozolomide Radionuclide Therapy Octreotate Lutetium-177 NeuroEndocrine Tumours Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 75
- 试验地点
- 4
- 主要终点
- Progression Free Survival
研究概览
简要总结
Two parallel phase II randomized open label trials of Lutetium-177 Octreotate (177Lu-Octreotate) peptide receptor radionuclide therapy (PRRT) and capecitabine (CAP)/temozolomide (TEM) chemotherapy (chemo): (i) versus CAPTEM alone in the treatment of low to intermediate grade pancreatic neuroendocrine tumours (pNETs); (ii) versus PRRT alone in the treatment of low to intermediate grade mid gut neuroendocrine tumours (mNETs).
详细描述
PROTOCOL SYNOPSIS
Background
Neuroendocrine tumours (NETs) are a heterogeneous group of malignancies that can arise at any site in the gastrointestinal tract, that are known by their ability to over express somatostatin receptors. Originally called carcinoid tumours, these tumours are rising in incidence. In patients with incurable disease, several systemic options have demonstrated activity but few have been compared in prospective, randomised controlled trials (RCTs). 177Lu-Octreotate peptide receptor radionuclide therapy (PRRT) and CAPTEM have shown promising activity in initial single arm trials. Prospective RCTs are needed to build on these early trials to determine the optimal role of these therapies in clinical practice.
CONTROL NETs is a parallel group phase II randomised open label trial of Lutetium-177 Octreotate (177Lu-Octreotate (Lutate)) peptide receptor radionuclide therapy (PRRT) and capecitabine (CAP)/temozolomide (TEM) chemotherapy (chemotherapy): (i) versus CAPTEM alone in the treatment of low to intermediate grade pancreatic neuroendocrine tumours (pNETs); (ii) versus PRRT alone in the treatment of low to intermediate grade midgut neuroendocrine tumours (mNETs).
General aim
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults ≥18 years old with histologically proven, moderate to well-differentiated G1/2 pancreatic or midgut NETs with Ki-67 < 20%;
- •The presence of somatostatin receptor avidity suitable for PRRT demonstrated on 68Ga-octreotate PET scan;
- •Progressive advanced/metastatic disease that has progressed during or after ≤ 2 prior systemic therapies;
- •Unresectable disease, determined by an appropriately specialized surgeon or deemed not suitable for liver directed therapies where liver is the only site of disease;
- •ECOG performance status 0-2;
- •Ability to swallow oral medication;
- •Adequate renal function (measured creatinine clearance > 50 ml/min by DTPA or 51CR-EDTA), bone marrow function (Hb > 9 g/d/L, ANC > 1.5 x109L, and platelets > 100 x 10/L);
- •Adequate liver function (serum total bilirubin ≤ 1.5 x ULN, and Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP) ≤ 2.5 x ULN (≤ 5 x ULN for patients with liver metastases)). INR ≤ 1.5 (or on a stable dose of LMW heparin for >2 weeks at time of enrolment .);
- •Life expectancy of at least 9 months;
- •Study treatment both planned and able to start within 28 days of randomisation; )
- •Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments;
- •Signed, written informed consent.
排除标准
- •Primary NETs other than small bowel (midgut) or pancreatic NETs;
- •Cytotoxic chemotherapy, targeted therapy, or biotherapy within the last four weeks;
- •Prior intrahepatic 90Y microspheres, such as SIR-Spheres in the past six months;
- •Prior Peptide Receptor Radionuclide Therapy;
- •Major surgery/surgical therapy for any cause within one month;
- •Surgical therapy of loco-regional metastases within the last three months prior to randomisation;
- •Uncontrolled metastatic disease to the central nervous system. To be eligible, CNS metastases should have been treated with surgery and/or radiotherapy and the patient should have been receiving a stable dose of steroids for at least 2 weeks prior to randomisation, with no deterioration in neurological symptoms during this time;
- •Poorly controlled concurrent medical illness. E.g. unstable diabetes (Note: optimal glycaemic control should be achieved before starting trial therapy); Symptomatic NYHA class III or IV congestive cardiac failure, myocardial infarction within 6 months of start of the study, serious uncontrolled cardiac arrhythmia, unstable angina, or any other clinically significant cardiac disease;
- •History of other malignancies within 5 years except where treated with curative intent AND with no current evidence of disease AND considered not to be at risk of future recurrence Patients with a past history of adequately treated carcinoma-in-situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or superficial transitional cell carcinoma of the bladder are eligible;
- •Any uncontrolled known active infection, including chronic active hepatitis B, hepatitis C, or HIV. Testing for these is not mandatory unless clinically indicated. Participants with known Hepatitis B/C infection will be allowed to participate providing evidence of viral suppression has been documented and the patient remains on appropriate anti-viral therapy;
- •Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of capecitabine/temozolomide (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or substantial small bowel resection);
- •Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule, including alcohol dependence or drug abuse;
- •Pregnancy, lactation, or inadequate contraception. Women must be post-menopausal, infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to registration. Men must have been surgically sterilised or use a (double if required) barrier method of contraception .
研究组 & 干预措施
PRRT
7.8GBq 177Lu Octreotate (Lutate) given intravenously (IV) on day 1 every 8 weeks for 4 cycles.
干预措施: octreotate (Drug)
CAPTEM
Oral capecitabine 750mg/m2 b.i.d. days 1-14 and temozolomide 75mg/m2 b.i.d. days 10-14 every 28 day cycle, up to 8 cycles.
干预措施: Capecitabine (Drug)
CAPTEM
Oral capecitabine 750mg/m2 b.i.d. days 1-14 and temozolomide 75mg/m2 b.i.d. days 10-14 every 28 day cycle, up to 8 cycles.
干预措施: Temozolomide (Drug)
PRRT/CAPTEM
7.8GBq 177Lu Octreotate (Lutate) given intravenously (IV) on day 10 every 8 weeks for 4 cycles, with concurrent oral capecitabine 750mg/m2 b.i.d. days 1-14 and temozolomide 75mg/m2 b.i.d. days 10-14 up to 4 cycles.
干预措施: octreotate (Drug)
PRRT/CAPTEM
7.8GBq 177Lu Octreotate (Lutate) given intravenously (IV) on day 10 every 8 weeks for 4 cycles, with concurrent oral capecitabine 750mg/m2 b.i.d. days 1-14 and temozolomide 75mg/m2 b.i.d. days 10-14 up to 4 cycles.
干预措施: Capecitabine (Drug)
PRRT/CAPTEM
7.8GBq 177Lu Octreotate (Lutate) given intravenously (IV) on day 10 every 8 weeks for 4 cycles, with concurrent oral capecitabine 750mg/m2 b.i.d. days 1-14 and temozolomide 75mg/m2 b.i.d. days 10-14 up to 4 cycles.
干预措施: Temozolomide (Drug)
结局指标
主要结局
Progression Free Survival
时间窗: 12 months for pNETs and 24 months for mNets
To determine the rate of progression free survival (PFS) at 12 months in pNETs (Group A), and at 24 months in mNETs (Group B). (PFS defined from time of randomisation to disease progression as defined by RECIST criteria version 1.1).
次要结局
- Objective tumour response rate (partial or complete response) as per RECIST v1.1 criteria(12 months or 24 months as appropriate)
- Safety (rates of adverse events worst grade according to NCI CTCAE v4.0)(12 months or 24 months as appropriate)
- Overall survival (death from any cause)(12 months or 24 months as appropriate)
- Resource utilisation (use of healthcare resources) and cost-effectiveness (Health utility score determined at beginning, during treatment and until end of follow up, correlated with MBS & PBS data)(12 months or 24 months as appropriate)
- Quality of life (QOL scores determined at beginning, during treatment and until disease progression)(12 months or 24 months as appropriate)
- Clinical Benefit(12 months or 24 months as appropriate)